Cancer of the large bowel is a leading cause of cancer morbidity and mortality in the United States. Our previous epidemiologic studies played a key role in documenting an inverse association between the use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDS) and the incidence of large bowel cancer. Those studies were inspired by laboratory data suggesting that NSAIDs may reduce colon carcinogenesis. Now a growing body of laboratory data indicates that the commonly used, relatively new class of cholesterol-lowering drugs, the "statins" may have a similar chemopreventive potential: statins inhibit the growth of colon cancer cells in vitro and in vivo. There is also some evidence that statins may enhance the chemopreventive effect of NSAIDS. The statins (e.g., lovastatin, simvastatin) were first marketed in 1987, and are now among the most commonly prescribed drugs in the United States. At this time there is little epidemiologic data concerning their potential protective effect against large bowel cancer. Two randomized trials of statin use as preventives of coronary heart disease had nonsignificant deficits of large bowel cancer in the treated groups. We propose to conduct a population-based case-control study in Massachusetts of the relation of statin use to the risk of large bowel cancer. We will identify 2050 incident cases aged 50-74 through participating hospitals and 2050 age, sex, and precinct matched community controls from Massachusetts town lists. Cases and controls will be interviewed to obtain information on demographic factors, risk factors for large bowel cancer, detailed histories of statin and NSAID use, and data useful for addressing potential biases. The study is large enough to assess the influence of characteristics of statin use (timing, duration, dose) on the risk of large bowel cancer and to assess consistency of findings across subgroups of age, sex, and cancer site. The joint effect of statins and NSAIDs will also be assessed. The proposed study will provide informative epidemiologic data on a potential chemopreventive of large bowel cancer. Because the incidence of the disease and prevalence of statin use by U.S. men and women are high, an inverse association would be of considerable public health importance. Moreover, it would shed light on a mechanism of colon carcinogenesis.